Identification of Putative Ortholog Gene Blocks Involved in Gestant and Lactating Mammary Gland Development: A Rodent Cross-Species Microarray Transcriptomics Approach
The mammary gland (MG) undergoes functional and metabolic changes during the transition from pregnancy to lactation, possibly by regulation of conserved genes. The objective was to elucidate orthologous genes, chromosome clusters and putative conserved transcriptional modules during MG development. We analyzed expression of 22,000 transcripts using murine microarrays and RNA samples of MG from virgin, pregnant, and lactating rats by cross-species hybridization. We identified 521 transcripts differentially expressed; upregulated in early (78%) and midpregnancy (89%) and early lactation (64%), but downregulated in mid-lactation (61%). Putative orthologous genes were identified. We mapped the altered genes to orthologous chromosomal locations in human and mouse. Eighteen sets of conserved genes associated with key cellular functions were revealed and conserved transcription factor binding site search entailed possible coregulation among all eight block sets of genes. This study demonstrates that the use of heterologous array hybridization for screening of orthologous gene expression from rat revealed sets of conserved genes arranged in chromosomal order implicated in signaling pathways and functional ontology. Results demonstrate the utilization power of comparative genomics and prove the feasibility of using rodent microarrays to identification of putative coexpressed orthologous genes involved in the control of human mammary gland development. 1. Introduction Mammals are the only animals that secrete a complex fluid from an elaborated skin gland to provide both innate protection and nourishment for their newborn. There are more than 4,000 species of mammals with striking similarities in the structure and function of their mammary glands as well as in their unique milk components such as the caseins, α-lactalbumin, lactoferrin, lactose, and milk fat. Nevertheless, variations are exhibited in the arrangement and numbers of mammary gland, milk composition, and suckling strategies. Mammary gland development begins at puberty and is maintained throughout pregnancy until lactation. During these last stages, development compromises numerous overlapping programs such as branching morphogenesis, inductive stromal-epithelial interactions, programmed cell death, extracellular matrix remodeling, and hormone action [1]. Current knowledge of the molecular regulation of mammary development and lactation has largely been derived from the dissection of signaling networks in cell culture systems and phenotypic characterization of genetically altered mice as well as
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